The long-term goal of our studies is to understand the molecular and genetic elements that underlie the process of aging and determine longevity. One of the most prominent hypotheses explaining the aging process is the oxidative stress hypothesis, which states that the rate of aging and life span is directly related to the accumulation of oxidative damage to organelles and macromolecules. Comparative studies between species having different life spans have been one of the foundations of the oxidative stress hypothesis, predicting a direct relationship between the accumulation of oxidative damage, the rate of aging and life span. We propose to use the fruit fly model system, Drosophila melanogaster, to compare the relationship between life span and the accrual of oxidative damage within a single, genetically well defined species, using a variety of strains and environmental and genetic conditions known to alter life span. These studies will better define the precise relationship between oxidative damage and life span, laying the foundation for a map detailing the specific quantitative relationship between oxidative damage, aging and life span. An additional advantage of using Drosophila to perform these comparative studies is that the powerful molecular and genetic techniques available in Drosophila can be used to directly identify and test specific physiological systems important in aging.